Safety/Tolerability and Pharmacokinetics/Pharmacodynamics of YH4808 After Oral Administration in Healthy Male Subjects

A Dose-block Randomized, Double-blind, Placebo/Active-controlled, Single/Multiple Dosing, Dose-escalation Phase I Clinical Trial to Investigate the Safety/Tolerability and PKs/PDs of YH4808 After Oral Administration in Healthy Male Subjects

First in human study

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: YH4808 30mg; Drug: YH4808 50mg; Drug: YH4808 100mg; Drug: YH4808 200mg; Drug: YH4808; Drug: YH4808 100mg (repeat dose); Drug: YH4808 200mg (repeat dose); Drug: YH4808 400 mg (repeat doses); Drug: YH4808 600mg; Drug: YH4808 800mg (single dose); Drug: Placebo; Drug: Esomeprazole 40mg

Detailed Description

Study to evaluate the safety and tolerability, pharmacokinetics/pharmacodynamics (PK/PD) parameters of an escalating, single dose/repeat doses of YH4808 in healthy subjects.

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Clinical trials center, Seoul national university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male volunteers in the age between 20 to 45 years old
• Subjects who were determined to be appropriate through screening
• Weight: over 50kg, within ±20% of ideal body weight
• Subjects who signed written consent after receiving thorough explanation on trial purpose, content, and characteristics of investigational drug

Exclusion Criteria:

• Clinically significant disorder in liver, kidney, cardiovascular, respiratory system, endocrine system and CNS in the physical examination and clinical laboratory tests or a medical history of malignant tumor or psychological disease
• Medical history of gastrointestinal disease or acid restraining surgery, gastric/esophagus surgery (excluding appendectomy, hernia surgery)
• A history of hypersensitivity to drugs or clinically significant allergic disease
• Clinically significant abnormal values in blood chemistry(≥ 1.5 fold of normal upper limit in the levels of SGOT, SGPT)
• Subjects who were unable to be applicable for pH meter catheter
• Subjects who had a history of drug abuse or who had a positive results on urine drug screening
• Subjects who had taken usual dose of any prescription drugs within 14 days before the treatment or who had used usual dose of OTC drugs within 7 days before the treatment(cf, be able to be enrolled in this study according to an investigatory consideration)
• Subjects who participated in another clinical trial within 3 months before enrolling in this study
• Subjects who donated whole blood within 2 months or component blood within 1 month or who are donated within 1 month before the treatment
• Subjects who drank Over 21 units/week of alcohol or subjects who weren't able to stop drinking alcohol during the hospitalization
• Subjects who stopped smoking within 3 months before the treatment
• Subjects who had a beverage containing grapefruits within 24hrs before the hospitalization or who had a beverage containing grapefruits during the hospitalization
• Subjects who had a beverage containing caffeine during the hospitalization
• H.pylori positive results on the Urease breath test(Only repeat doses)
• Subjects with clinically significant observations considered as unsuitable based on medical judgment by investigators

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 10 volunteers will be administered matched placebo.; Other Names: 10 volunteers will be administered matched placebo.
Experimental: YH4808 30mg; 1.Single dose 2.12 volunteers were administered YH4808 30mg or active/placebo comparators.(YH4808:active:placebo=8:2:2)	Drug: YH4808 30mg; YH4808 30mg (single dose); Other Names: YH4808 30mg (single dose)
Experimental: YH4808 50mg; 1.Single dose 2.12 volunteers were administered YH4808 50mg or active/placebo comparators.(YH4808:active:placebo=8:2:2)	Drug: YH4808 50mg; YH4808 50mg (single dose); Other Names: YH4808 50mg (single dose)
Experimental: YH4808 100mg; 1.Single dose 2.12 volunteers were administered YH4808 100mg or active/placebo comparators.(YH4808:active:placebo=8:2:2)	Drug: YH4808 100mg; YH4808 100mg (single dose); Other Names: YH4808 100mg (single dose)
Experimental: YH4808 200mg; 1.Single dose 2.12 volunteers were administered YH4808 200mg or active/placebo comparators.(YH4808:active:placebo=8:2:2)	Drug: YH4808 200mg; YH4808 200mg (single dose); Other Names: YH4808 200mg (single dose)
Experimental: YH4808 400mg; 1.Single dose 2.12 volunteers were administered YH4808 400mg or active/placebo comparators.(YH4808:active:placebo=8:2:2)	Drug: YH4808; YH4808 400mg (single dose); Other Names: YH4808 400mg (single dose)
Experimental: YH4808 100mg(repeat doses); 1.Repeat doses 2.12 volunteers were administered YH4808 100mg or active/placebo comparators.(YH4808:active:placebo=8:2:2)	Drug: YH4808 100mg (repeat dose); YH4808 100mg (repeat dose)
Experimental: YH4808 200mg(repeat doses); 1.Repeat doses 2.16 volunteers were administered YH4808 200mg or active/placebo comparators.(YH4808:active:placebo=8:6:2)	Drug: YH4808 200mg (repeat dose); YH4808 200mg (repeat dose)
Experimental: YH4808 400mg(repeat doses); 1.Repeat dose 2.12 volunteers were administered YH4808 400mg or active/placebo comparators.(YH4808:active:placebo=8:2:2)	Drug: YH4808 400 mg (repeat doses); YH4808 400 mg (repeat doses)
Experimental: YH4808 600mg; 1.Single dose 2.12 volunteers were administered YH4808 600mg or active/placebo comparators.(YH4808:active:placebo=8:2:2)	Drug: YH4808 600mg; YH4808 600mg
Experimental: YH4808 800mg; 1.Single dose 2.12 volunteers were administered YH4808 800mg or active/placebo comparators.(YH4808:active:placebo=8:2:2)	Drug: YH4808 800mg (single dose); YH4808 800mg (single dose)
Active Comparator: Esomeprazole 40mg	Drug: Esomeprazole 40mg; 24 volunteers will be administered Esomeprazole 40mg; Other Names: 24 volunteers will be administered Esomeprazole 40mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the PKs, PDs, safety and tolerability of escalating, single/multiple oral doses of YH4808	Throughout the study

Collaborators and Investigators

• Sponsor: Yuhan Corporation

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: November 2, 2009
• First Submitted That Met QC Criteria: November 2, 2009
• First Posted (Estimate): November 3, 2009

Study Record Updates

• Last Update Posted (Estimate): July 10, 2014
• Last Update Submitted That Met QC Criteria: July 8, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Safety, tolerability and PK/PD
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole
• Other Study ID Numbers: YCD142 (YH4808-101)